The objectives of this contract are to determine the in vivo efficacy of novel compounds in a animal model of relapse, including the following tests in animals trained to self-administer cocaine; (1) the ability of a test compound to block footshock- or other stressor-induced reinstatement of responding after a period of experimental extinction, (2) the ability of a test compound to block cocaine-priming-induced reinstatement of responding after a period of extinction, and (3) the ability of a test compound to block the effects of a conditioned cue (previously paired with cocaine) to reinstate responding for cocaine after a period of extinction. The development of methods, and the design, evaluation, and implementation of protocols is understood to be an integral part of this work, because although all of the methodologies have been described in the literature, some of them have been used in only a few laboratories and with variable success. This contract shall also support follow-up rodent pharmacology studies of compounds identified as promising potential drug-dependence treatment agents. The details of these latter studies cannot be specified in advance of contract award; they will depend upon specific successes in NIDA's medication discovery efforts and scientific advances in the general field of drug abuse research. The anticipated end results of this contract are written reports detailing study findings that will be used by the Cocaine Treatment Discovery Program of the Division of Treatment Research and Development.